Distinct Role of Specialized Cutaneous Schwann Cell Network in Acute and Chronic Pain Sensation
Shan‑Xin Zhang1,2,3 · Jing Yang3,4 · Yao Lou1,5 · Song‑Cheng Xu1 · Ran Guo1,5 · Zhen‑Zhong Xu2,3,6
1 Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, China
2 Nanhu Brain–Computer Interface Institute, Hangzhou 311100, China
3 School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China
4 Department of Anesthesiology, Ningbo Second Hospital, Ningbo 315010, China
5 Center for Rehabilitation Medicine, Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, China
6 Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain‑machine Integration, State Key Laboratory of Brain‑machine Intelligence, Zhejiang University, Hangzhou 311121, China
Abstract
Specialized cutaneous Schwann cells (scSCs) are a recently identified glial class implicated in cutaneous pain modulation, yet their three-dimensional architecture and role in chronic pain remain unclear. Using tissue optical clearing, we reconstructed the 3D morphology of scSCs, revealing an intricate mesh-like network, with extensive branching penetrating the epidermal layer and establishing close associations with A- and C-fiber primary sensory nerve terminals. Optogenetic activation of scSCs elicited nociceptive reflex behaviors, dependent on concurrent A- and C-fiber activation, but not affective-motivational responses. We further investigated the morphological and functional alterations of scSCs in chronic inflammatory pain and neuropathic pain models. Interestingly, scSCs were found to play a partial role in modulating nociceptive behaviors but not aversions in chronic pain. Together, these findings provide new insights into the functional dynamics of scSCs in nociceptive signal processing and their limited contribution to chronic pain states.
Keywords
Specialized cutaneous Schwann cells; Chronic pain; Tissue optical clearing; Optogenetics
